Polymer-supported silyl enol ethers

Reagents and conditions i) R CH COSK, DMF ii) TMSOTf, NEtj, CHsClai iii) imine, Sc(OTf)3 (10 nwRi), GHjClj iv) LiBH4, Et O, r.t. 

Starting from commercially available Merrifield resin, silyl enol ether 57 was generated in two steps. Lewis acid catalysed addition of 57 to a variety of imines gave amino thioesters 58 which upon reduction with LiBH afforded amino alcohols 59 in moderate to good yields (50-80%). After reduction, the resin was recovered in its thiol form and could be further acylated and re-used. 

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Silyl enol ethers are versatile reagents in organic synthesis [83]. They are used as isol-able enolate equivalents and many useful reactions have been developed using silyl enol ethers [83]. As a new approach to exploit an efficient method for combinatorial synthesis [84], silyl enol ethers were successfully immobilized on to a polymer. Polymer-supported silyl enol ethers (PSSEEs) were prepared according to Sch. 10 [85]. In aldol reactions of PSSEEs with aldehydes, it was again found that Sc(OTf)3 was an efficient catalyst [86]. An example of the preparation of a 1,3-diol library by use of PSSEEs is shown in Sch. 11. In all cases, the reactions proceeded smoothly to afford the corresponding 1,3-diols in good yields. 1,3-Diols are successfully cleaved from the... 

Scheme 10. Synthesis of polymer-supported silyl enol ethers.

A library of y-amino alcohols has been synthesised using polymer-supported silyl enol ethers. The strategy followed by Kobayashi et al - is outlined in Scheme 3S.2. 

Polymer-supported silyl enol ethers (PSSEEs) can be employed in Sc(OTf)3-catalyzed reactions with aldehydes and aromatic amines. This process provides a convenient method for the construction of a /8-amino alcohol library. 

Mannich-type Reactions. The reactions of imines with ketene silyl acetals proceed smoothly in the presence of Sc(OTf)3 to afford the corresponding 8-amino ester derivative in moderate yield (eq 6). Sc(OTf)3 shows higher activity than Yh(OTf)3 does in this case. The catalyst can be recovered after the reaction is corrqilete and reused. A Mannich-type reaction of N-( 8-aminoalkyl)benzotriazoles with silyl enolates has also been developed.Mannich-type reactions of polymer-supported silyl enol ethers with imines or of polymer-supported a-iminoaceta-tes with silyl enolates are also catalyzed by Sc(OTf)3. 

Kob1996a Kobayashi, S., Hachiya, I. and Yasuda, M., Aldol Reactions on Solid Phase. Sc(OTf)3-Catalyzed Aldol Reactions of Polymer-Supported Silyl Enol Ethers with Aldehydes Providing Convenient Methods for the Preparation of 1,3-Diol, P Hydroxy Carboxylic Acid, and jS-Hydroxy Aldehyde Libraries, Tetrahedron Lett., 37 (1996) 5569-5572. 

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

Chiral lithium amide bases have been used successfully in the asymmetric deprotonation of prochiral ketones [55, 56]. WUliard prepared polymer-supported chiral amines from amino acid derivatives and Merrifield resin [57]. The treatment of cis-2,6-dimethylcyclohexanone with the polymer-supported chiral lithium amide base, followed by the reaction with TMSCl, gave the chiral silyl enol ether. By using polymeric base 96, asymmetric deprotonation occurred smoothly in tetrahydrofuran to give the chiral sUyl enol ether (, S )-102 in 94% with 82% ee (Scheme 3.28). 

Mannich reaction. This reagent and similar rr-acids on polymer support effect chemoselective condensation between silyl enol ethers and imines in refluxing MeCN aldehydes do not participate in the reaction. 

Scandium triflate-catalyzed aldol reactions of silyl enol ethers with aldehyde were successfully carried out in micellar systems and encapsulating systems. While the reactions proceeded sluggishly in water alone, strong enhancement of the reactivity was observed in the presence of a small amount of a surfactant. The effect of surfactant was attributed to the stabiMzation of enol silyl ether by it. Versatile carbon-carbon bondforming reactions proceeded in water without using any organic solvents. Cross-linked Sc-containing dendrimers were also found to be effective and the catalyst can be readily recycled without any appreciable loss of catalytic activity.Aldol reaction of 1-phenyl-l-(trimethylsilyloxy) ethylene and benzaldehyde was also conducted in a gel medium of fluoroalkyl end-capped 2-acrylamido-2-methylpropanesulfonic acid polymer. A nanostmctured, polymer-supported Sc(III) catalyst (NP-Sc) functions in water at ambient temperature and can be efficiently recycled. It also affords stereoselectivities different from isotropic solution and solid-state scandium catalysts in Mukaiyama aldol and Mannich-type reactions. 

CB1981] and the same reaction of the related silyl enol ether (16) using polymer supported mandelic acid leads to (5)-mandelic acid in up to 94% e.e. [94TL2891]. Low temperature protonation of the anion derived from (17) produces mainly the cis product by kinetic control [94CB1495] and hydroboration of (18) gives the cis hydroxymethyl compound with high... 

Based on Mannich-type reactions of N-acryliminoacetates with silyl enol ethers, a new method for the preparation of N-acylated amino acid derivatives via nucleophilic addition to N-acrylimino ester has been developed using a polymer-supported amine and scandium catalysts (Scheme 12.5) [9]. Ethyl N-benzoyl-2-bromoglycine was used as a substrate. It could be readily converted to reactive N-acrylimino ester in situ by treatment with a base. Immobilizations of the amine and the scandium species into polymeric supports prevented loss of activity of the catalyst. The method is simple and provides a convenient method for the preparation of N-acrylated amino acid derivatives. 

A hydrophobic polymer-supported scandium(III) catalyst was also successfully used in the Michael reaction of unsaturated ketones with silyl enol ethers. Recently, an amphiphilic resin-supported rhodium/phosphine complex was used as catalyst in the 1,4-addition of various boronic acids to enones in water at 25°C. High yields were obtained and the catalyst was easily separated and subjected to a second and third round of reactions with no decrease in activity. ... 

Oohara T, Nambu H, Anada M, Takeda K, Hashimoto S. A polymer-supported chiral fluorinated dirhodium(II) complex for asymmetric amination of silyl enol ethers. Adv Synth Catal. 2012 354 2331-2338. 

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